Fetal alcohol spectrum disorder (FASD) includes a constellation of symptoms and deficits in social behavior has become acknowledged as possibly one of the most debilitating symptoms. However, the behavioral and neural mechanism giving rise to the social deficits seen in FASD and the degree to which the environment plays a role in these social deficits remains unknown. Thus, the environment of alcohol-exposed pups will be modified such that they are exposed to intensive norma social interactions during development, isolation during the juvenile period, and abnormal mothering behavior in order to examine mitigating or exacerbating factors in the social deficits. Interactions of environment will be examined across different doses of alcohol, with the prediction that effects of low doses of alcohol will be more sensitive to environmental manipulations. Based on evidence from this laboratory and others, it is hypothesized that the ethanol-induced social deficits might arise from changes in mu opioid system. This hypothesis is examined using autoradiography and microinjectior techniques. Behavioral analyses of the social deficits observed in animals exposed to alcohol during development has demonstrated that the deficits are not likely due to changes in social motivationanc some evidence suggests that there are deficits in the ability to process social cues. The social response of animals to different gradations of sensory cues and the ability to detect social cues inthe olfactory, auditory and somatosensory domains will be examined. Using the additive factors method, the contribution of deficits in social cue processing to social deficits in general in ethanol-exposed animals will be determined. c-Fos immunoreactivity will be used to examine the neural structures contributing to the sensory processing deficit. The rat model of FASD used in this proposal entails exposure during both the prenatal and postnatal period, mimicking the effect of alcohol exposure during all three trimesters in the humans. FASD continues to be a public health problem occurring large expenses both to society and the individual. The proposed studies will use a rat model of FASD to delineate the behavioral and neurobiological mechanism underlying the social deficits in this disorder and the contribution of social environments to the impact of ethanol during development. These findings can then be translated into both biological and behavioral treatments for FASD. PERFORMANCE S\TE(S)(organization, city, state) Department of Psychology University of South Carolina Columbia, SC PHS 398 (Rev. 09/04) Page 2 Form Page 2 Principal Investigator/Program Director (Last, first, middle): KELLY, Sandra, Jean KEY PERSONNEL. See instructions. Use continuation pages as needed to provide the required information in the format shown below. Start with Principal Investigator. List all other key personnel in alphabetical order, last name first. Name eRA Commons User Name Organization Role on Project KELLY, Sandra,J. SJKELLY University of South Carolina PrincipalInvestigator OTHER SIGNIFICANT CONTRIBUTORS Name Organization Role on Project Sweitzer, Sarah, M. University of South Carolina Consultant School of Medicine Human Embryonic Stem Cells Bl No D Yes If the proposed project involves human embryonic stem cells, list below the registration number of the specific cell line(s) from the following lis http://stemcells.nih.gov/reqistrv/index.asp. Usecontinuation pages as needed. If a specific line cannot be referenced at this time, include a statement that one from the Registry will be used. Cell Line Disclosure Permission Sfate/nenf.Applicable to SBIR/STTR Onlv.See Instructions. fZlYes DlMo PHS 398 (Rev. 09/04) Page2-continued Form Page 2-continued Number the following pages consecutively throughout the application. Do not use suffixes such as 4a, 4b. Principal Investigator/Program Director (Last, first, middle): KELLY, Sandra, Jean The name of the principal investigator/program director must be provided at the top of each printed page and each continuation page. RESEARCH GRANT TABLE OFCONTENTS P"e Numbers Face Page 1 Description,